POS0760 LONG-TERM PROGNOSTIC FOLLOW-UP OF PATIENTS WITH REFRACTORY SYSTEMIC JUVENILE IDIOPATHIC ARTHRITIS AFTER THE CLINICAL TRIAL OF TOCILIZUMAB AS A FIRST-LINE BIOLOGIC TREATMENT
Authors: T. Miyamae, T. Kawabe, K. Nishimura, S. Hattori, T. Imagawa, T. Ishii, S. Ito, N. Iwata, Y. Kamata, Y. Kamiyama, M. Mizuta, M. Mori, A. Murase, Y. Nakagishi, T. Nakano, S. Nakayamada, T. Nozawa, T. Ohya, N. Okamoto, K. Sato, Y. Sugita, S. Takei, Y. Tanaka, M. Tomiita, H. Umebayashi, Y. Yamasaki, N. Nishimoto, S. Yokota
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Tocilizumab (TCZ) was approved for systemic juvenile idiopathic arthritis (sJIA) as an intravenous formulation in 2008 after its effectiveness and safety were shown in a world-leading clinical trial performed in Japan in 2002–2008. <h3>Objectives</h3> This study aimed to understand the long-term prognosis of patients participating in phases II (Study MRA011JP), III (Study MRA316JP), and III/IV (Study MRA324JP). There were 149 participants in the clinical trial. <h3>Methods</h3> Information on eligible patients was obtained from 12 cooperating institutions approved by the Ethics Committee of Tokyo Women's Medical University and each institution. Patients who could be followed-up were referred and transferred to other hospitals or departments. The following long-term prognoses were assessed: treatment status, including the continuation of TCZ administration during the long-term course of sJIA, disease status (remission rate and clinical phenotype), complications, social adjustment, employment status, and <i>health-related</i> quality of life (HRQOL) scale. <h3>Results</h3> Results were collected for 132 cases from ten centers by December 2022. We examined 125 patients (58 males and 67 females) whose medical records were still available and whose final diagnosis was sJIA. The age of the study participants was 18.6 years at the time of the study, 4.3 years at onset, 8.8 years at first TCZ administration, 3.8 years from onset to the first TCZ administration, and 9.1 years from TCZ initiation (all median values). Of the 125 patients, 28 (22.4%) were in medication-free remission and were either under or completely followed-up. Of the 93 patients (74.4%) who continued therapy, 10 (10.8%) were moved to a subcutaneous version of TCZ, which is not yet licensed for the treatment of sJIA in Japan. Ten patients (10.8%) were switched to canakinumab (CAN) due to TCZ primary failure (5 patients), secondary failure (2 patients), side effects (1 patient developed anaphylaxis), or other reasons. Of the 124 patients, 44 (35.5%) changed from acute febrile sJIA to chronic arthritic sJIA, in which chronic arthritis was the primary pathology without systemic inflammation, and 17 of these patients still had active arthritis at the last observation. Corticosteroids were prescribed in 54 of 93 patients (58.1%). Except in one case of sudden death, the causes of death in the four cases that resulted in fatalities were macrophage activation syndrome, sJIA-related interstitial pneumonia, and disseminated aspergillosis. The most commonly observed complications were osteoporosis in 68 (54.4%), infection requiring hospitalization in 32 (25.6%), and hypertension in 25 (20%). The EQ-5D-5L score was 0.91 (mean). The final mean height of the patients whose information was available after the age of 18 years (n = 62) was 157.7 cm for males (mean 170.4 cm in Japanese) and 144.3 cm for females (mean 156.7 cm in Japanese), showing a significant short stature. The college/university enrollment rate was as high as 68.4% (Japanese statistical data: 58.9%), and all but five students were employed. <h3>Conclusion</h3> Seventy-four percent of the patients continued treatment with TCZ or CAN, and conversion to chronic arthritic sJIA was observed in 35.5%. Despite issues such as growth retardation, social adjustment and employment status were promising, suggesting a contribution of treatment. <h3>Reference</h3> [1]Yokota S, et al. Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis: a randomized, double-blind, placebo-controlled, withdrawal phase III trial. Lancet. 2008 Mar 22;371(9617):998-1006. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Takako Miyamae Speakers bureau: TM has received speaker's fee from AbbVie Japan GK, Ayumi Pharmaceutical Co., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Novartis Japan, Pfizer Japan Inc. , Tomohiro Kawabe: None declared, Kenichi Nishimura Speakers bureau: Novaritis Pharma, Grant/research support from: Chugai Pharma, Seira Hattori Grant/research support from: Chugai Pharma, Tomoyuki Imagawa: None declared, Tomonori Ishii Speakers bureau: Paid as speaker, chugai, Shuichi Ito Paid instructor for: Novaritis Pharma, Chugai Pharma, Grant/research support from: Chugai Pharma, Naomi Iwata: None declared, Yasuyuki Kamata: None declared, Yuji Kamiyama Grant/research support from: Chugai Pharma, Mao Mizuta Speakers bureau: Novartis Pharma K.K., Masaaki Mori Speakers bureau: I have received lecture fees from MSD, Chugai, UCB Japan, Abbvie Japan, Japan Blood Products Organization, AYUMI, and Asahi-Kasei., Grant/research support from: I belong to the department that is financially supported by Chugai, UCB Japan, CSL Behring, Abbvie Japan, Japan Blood Products Organization, AYUMI, Nippon Kayaku, and Asahi-Kasei., Ayako Murase Grant/research support from: Chugai Pharma, Yasuo Nakagishi Speakers bureau: CHUGAI PHARMACEUTICAL CO.,LTD. Novartis Pharma K.K. AstraZeneca plc, Taiji Nakano Grant/research support from: Maruho Co., Ltd 500,000 yen, Torii Pharmaceutical Co., Ltd 300,000 yen, Shingo Nakayamada Speakers bureau: S Nakayamada has received consulting fees, lecture fees, and/or honoraria from Bristol-Myers, AstraZeneca, Pfizer, GlaxoSmithKline, AbbVie, Astellas, Asahi-kasei, Sanofi, Chugai, Eisai, Gilead Sciences, Boehringer Ingelheim., Grant/research support from: S. Nakayamada has received research grants from Mitsubishi-Tanabe, Tomo Nozawa Grant/research support from: Chugai Pharma, Takashi Ohya Grant/research support from: Chugai Pharma, Nami Okamoto Speakers bureau: N.O. has received honoraria or lecture fees from AbbVie Inc.; Amgen Inc.; Asahi Kasei Pharma Corporation; Astellas Pharma Inc.; AstraZeneca PLC; AYUMI Pharmaceutical Co., Ltd.; Bristol Myers Squibb; Chugai Pharmaceutical Co., Ltd.; Eisai Co., Ltd.; Eli Lilly Japan K.K.; GlaxoSmithKline PLC; Mitsubishi Tanabe Pharma Corporation; Novartis Pharma K.K.; Pfizer Inc.; and Teijin Pharma Limited;., Paid instructor for: N.O. has has received consulting fees from Daiichi Sankyo Company Limited; Eli Lilly Japan K.K.; and Swedish Orphan Biovitrum AB, Kojiro Sato Speakers bureau: Chugai Pharmaceutical Co., Ltd, One time, 100,000 yen, Grant/research support from: Chugai Pharmaceutical Co., Ltd, Four times, average 1,800,000 yen, Yuko Sugita: None declared, Shuji Takei Speakers bureau: Glaxo Smith Klein Pharmaceuticals Ltd, Novartis Pharma K.K., AbbVie, Mitsubishi Tanabe Pharma Corporation, Ayumimi Pharmaceutical Co, Bristol-Myers Squibb, Eli-Lilly,K.K., Asahi Kasei Medical Co., Sanofi, K.K., Grant/research support from: Chugai Pharcaceutical Co.Ltd., Eisai Co.Ltd., Yoshiya Tanaka Speakers bureau: Y. Tanaka has received speaking fees and/or honoraria from Behringer-Ingelheim, Eli Lilly, Abbvie, Gilead, AstraZeneca, Bristol-Myers, Chugai, Daiichi-Sankyo, Eisai, Pfizer, Mitsubishi-Tanabe, GlaxoSmithKline, Grant/research support from: Y. Tanaka has received research grants from Asahi-Kasei, Abbvie, Chugai, Eisai, Takeda, Daiichi-Sankyo, Behringer-Ingelheim., Minako Tomiita: None declared, Hiroaki Umebayashi Speakers bureau: Novartis, Yuichi Yamasaki: None declared, Norihiro Nishimoto Speakers bureau: I have been paid as a speaker for Chugai Pharmaceutical Co. Ltd.,the product company of tocilizumab., Paid instructor for: I have been a paid instructor for Chugai Pharmaceutical Co. Ltd.,the product company of tocilizumab., Consultant of: I have been work as a paid consultant for Chugai Pharmaceutical Co. Ltd.,the product company of tocilizumab., Grant/research support from: I have received financial grants from Chugai Pharmaceutical Co. Ltd.,the product company of tocilizumab., Shumpei Yokota: None declared.